Chiral surfactant

Novel chiral. separations using enzymes and chiral surfactants as carriers have been realized using facilitated transport membranes. Japanese workers have reported the synthesis of a novel norbornadiene polymeric membrane with optically active pendent groups that show enantio.selectivity, which has shown promi.se in the. separation of propronalol. 

Capillary electrophoresis employing chiral selectors has been shown to be a useful analytical method to separate enantiomers. Conventionally, instrumental chiral separations have been achieved by gas chromatography and by high performance liquid chromatography.127 In recent years, there has been considerable activity in the separation and characterization of racemic pharmaceuticals by high performance capillary electrophoresis, with particular interest paid to using this technique in modem pharmaceutical analytical laboratories.128 130 The most frequently used chiral selectors in CE are cyclodextrins, crown ethers, chiral surfactants, bile acids, and protein-filled... 

Chiral surfactants have been used in the aqueous chiral micellar catalysis of a Diels-Alder reaction using an (5)-leucine-derived surfactant (Figure 12.4) to catalyze the reaction between cyclopentadiene and nonyl acrylate.65... 

On two previous occasions we have reviewed the behavior of chiral surfactants at the air-water interface first as an introduction to the... 

The implications for films cast from mixtures of enantiomers is that diagrams similar to those obtained for phase changes (i.e., melting point, etc.) versus composition for the bulk surfactant may be obtained if a film property is plotted as a function of composition. In the case of enantiomeric mixtures, these monolayer properties should be symmetric about the racemic mixture, and may help to determine whether the associations in the racemic film are homochiral, heterochiral, or ideal. Monolayers cast from non-enantiomeric chiral surfactant mixtures normally will not exhibit this feature. In addition, a systematic study of binary films cast from a mixture of chiral and achiral surfactants may help to determine the limits for chiral discrimination in monolayers doped with an achiral diluent. However, to our knowledge, there has never been any other systematic investigation of the thermodynamic, rheological and mixing properties of chiral monolayers than those reported below from this laboratory. 

Our first investigations of the stereospecific aggregation of molecules in a monolayer involved the use of a novel chiral surfactant, AT-(a-methylbenzyl)stearamide, spread on aqueous acid subphases (Arnett and Thompson, 1981 Arnett et al, 1982). This surfactant was chosen for study because of the potential for strong hydrogen bonding between enantiomers, which should in theory yield closely packed aggregates in a film system. 

Phospholipids are perhaps the most ubiquitous of chiral surfactants in cell biology. It is well known that only the L-isomer is naturally occurring in the cell membrane of most living organisms, yet the question of whether or not this homochirality plays a role in the regulation of cell chemistry has barely... 

Table 2 Lift-off areas per molecule for different chiral surfactants studied at 25°C on a pure water subphase.

Despite the clear evidence of stereodifferentiation exhibited in the W/A isotherms of these chiral surfactants, the instabilities of the films as spread from solution at temperatures of experimental feasibility prevent a thorough description of the factors that might lead to molecular recognition in monolayers at equilibrium with their environments. Our next line of approach to this problem has been to conduct a broad investigation of the most attractive candidate from this group. 

Generally speaking imidazole is the nucleophilic functional group, and many of the chiral surfactants are histidine derivatives (Brown and Bunton, 1974 Brown et al., 1981). In other cases mixed systems have been used, e.g. an inert cationic surfactant plus a chiral amphiphilic histidine or hydroxa-... 

Deacylation of p-nitrophenyl derivatives of amino acids Chiral surfactants derived from amino acids. Comparisons of rates and enantioselectivities Ono etal., 1981... 

S. Fireman-Shoresh, S. Marx and D. Avnir, Enantioselective Sol-Gel Materials Obtained by Either Doping or Imprinting with a Chiral Surfactant, Adv. Mater., 2001, 19, 2145. 

A more substantial example of stereoselective catalysis was reported by Brown and Bunton (1974). Hydrolysis of (R)- and (5)-[37] was promoted by the micelle of chiral surfactant [381 in an enantioselective manner. The... 

Although similar efforts have been devoted to related polymer systems (Overberger and Cho, 1968 Overberger and Dixon, 1977 Okamoto, 1978), large enantioselectivity has not been observed. Goldberg et al. (1978) conducted borohydride reduction of phenyl ketones in micelles of the chiral surfactant [44]. The result was disappointing, since the maximal enantioselectivity was only 1.66% for phenyl propyl ketone. A much better optical yield was reported when this reaction was carried out under phase-transfer conditions (Masse and Parayre, 1976). The cholic acid micelle and bovine serum albumin exhibited the relatively high enantioselectivity in the reduction of trifluoroacetophenone (Baba ef al., 1978). 

The ability of a chiral molecule to distinguish between the enantiomers of a second (different) chiral molecule was defined in Sect. II as a diastereomer discrimination. This phenomenon may be observed in a mixed monolayer of two chiral surfactants and may also occur when a chiral substance is dissolved in the aqueous subphase under the monolayer of a second chiral substance. As before, examples of such chiral discrimination would not include those whose difference in monolayer behavior results only from the gross structural differences of diastereomers such as the different force-area characteristics exhibited by mixed monolayers of l-oleoyl-2-stearoyl-3-s -phospha-tidylcholine with epimeric steroids (120). The relevant experiment, that of comparing the monolayer behavior of mixed monolayers of cholesterol with enantiomeric phospholipids, has been reported (121). As might be anticipated from our previous discussion of... 

Probably the most interesting and important example of diastere-omer discrimination known to us is part of the body of work conducted by Monica Lundquist, whose enormous contribution to the area of chiral discrimination in monolayers is discussed in Sect. V. In her third paper (79), she demonstrated that Fredga s method of quasi-racemates (33) can be appUed to the two-dimensional organization of chiral surfactants in monolayers. 

The force-area curves for racemic and (5 )-(+>2-tetracosanyl acetate were shown in Figures 17 and 18, respectively, while those of methyl esters of racemic and (5 )-(+)-2-methylhexacosanoic acid are found in Figs. 21 and 22, respectively. All these curves were obtained under identical experimental conditions at thevarious temperatures indicated in the figures. Simple inspection shows that the force-area curves of the two racemic samples are very similar, as are those for both optically pure samples. Lundquist suggested that this is merely a result of the very similar shapes and molecular structures of these chiral surfactants. Apart from the chain length, the only structural difference is limited to a reversal of the positions of the carbonyl group and ester oxygen. 

In summary, it can be stated that for screening approaches in CE, only CD derivatives have been used. Other chiral selectors occasionally applied in CE, such as crown ethers, macrocyclic antibiotics, and chiral surfactants [39], were not found to be involved in (generic) screening approaches for chiral separations. 

Newly used chiral surfactants often have a low critical micellar concentration, are highly soluble and can be synthesized both in L- and D-forms. This last feature makes it possible to easily change the migration order of the optical isomers, which is very interesting for the determination of the optical pnrity of drugs, where for quantification purposes it is favorable that the chiral impurity migrates before the main component. 

Based on the theory, the separation of enantiomers requires a chiral additive to the CE separation buffer, while diastereomers can also be separated without the chiral selector. The majority of chiral CE separations are based on simple or chemically modified cyclodextrins. However, also other additives such as chiral crown ethers, linear oligo- and polysaccharides, macrocyclic antibiotics, chiral calixarenes, chiral ion-pairing agents, and chiral surfactants can be used. Eew non-chiral separation examples for the separation of diastereomers can be found. 

Shamsi, S. A. (2001). Micellar electrokinetic chromatography-mass spectrometry using a polymerized chiral surfactant. Anal. Chem. 73, 5103-5108. 

MEKC is also performed using cationic, nonionic, and zwitterionic surfactants. Widely employed are cationic surfactant consisting of a long chain tetralkylammonium salt, such as cetyltrimeth-ylammonium bromide, which causes the reversal of the direction of the EOE, due to the adsorption of the organic cation on the capillary wall. Other interesting options include the use of mixed micelles resulting from the simultaneous incorporation into the BGE of ionic and nonionic or ionic and zwitterionic surfactants. Chiral surfactants, either natural as bile salts [207] or synthetic [208] are employed for enantiomer separations. 

The chiral-bilayer-effect hypothesis has been evoked for the rationalization of the helical fibers formed from enantiomeric or diastereomeric surfactants (Fig. 54) [373], Different packing of the chiral surfactants in the crystals (head-to-tail) and in bilayer or micellar aggregates (tail-to-tail) is the basis for this postulate. Crystallization from aggregates requires an energetically costly, 180°... 

In general, it has been argued that tubular morphology is an expression of the chirality of the monomeric species, though there are a number of examples of non-chiral surfactants (such as the dimorpholinophospho-amidate 5) that have been shown to self-assemble into such structures.78,79 In some contradictory reports it is even argued that chirality is a requirement and that cylinders are in fact sheet-like structures that are curled.69... 

Chiral micellar solubilization may involve the use of chiral surfactants, or a combination of achiral surfactants and a chiral selector. Terabe [26] and Bereuter [25] provide a comprehensive overview of applications involving chiral surfactants such as bile salts or synthetic amino acid surfactants. The use of cyclodextrins (CD) as the chiral selector in combination with MEKC was successful for the separation of neutral racemic nonsteroidal aromatase inhibitors and barbituates [38]. Further approaches to the separation of enantiomers utilizing a combination of CD-MEKC have been described in the review by Terabe [26]. 

In MECC anionic surfactants are most frequently used, but cationic surfactants are also very popular. In addition, chiral surfactants, nonionic surfactants, zwitterionic surfactants, biological surfactants, or mixtures of each are finding increasing use. In all categories, variations in alkyl chain length will affect resolution or selectivity, as will changes in buffer concentration, pH, and temperature or the use of additives such as metal ions or organic modifiers. Typical surfactant systems used in MECC are shown in Table 5.3. 

If the standard operating conditons do not provide the required separation, selectivity can be modified by changing a number of variables, including the nature of the surfactant and the aqueous phases. Altering the hydrophilic end of the surfactant has a dramatic effect since this is the end of the micelle that interacts with the solutes. Alternatively, a second surfactant can be added to form a mixed micelle. The addition of a nonionic surfactant to an ionic one decreases the migration time window so that the migration time of all the analytes decreases nonionic chiral surfactants are often added to MECC buffers for the separation of enantiomers. 

The use of mixed micelles for chiral recognition was discussed in Section 5.3.3, using cyclodextrins. In addition to cyclodextrins, however, metal-amino acid complexes can also be used in a mixed mode arrangement. Bile salts are naturally occurring chiral surfactants that can be used as alternatives to, or in addition to, SDS for chiral recognition. In the presence of SDS, the migration times are faster. Table 5.5 shows initial operating conditions that can be used in chiral CE as a start to methods development.40... 

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